N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3
antagonist identified from a series of compounds with higher pA2
(7.6) and good log P (2.91) value was screened in rodent models of depression
such as forced swim test (FST), tail suspension test (TST), interaction studies
with standard anti-depressants and confirmatory studies such as reversal of
parthenolide induced depression and reserpine induced hypothermia. In FST (2
and 4 mg/kg) and TST (2 and 4 mg/kg), QCM-13 significantly reduced the duration
of immobility in mice without affecting the base line locomotion. QCM-13 (2 and
4 mg/kg) was also found to have significant interaction with standard
anti-depressants (fluoxetine and bupropion in FST and TST respectively).
Further, reversal of parthenolide induced depression in mice and reserpine
induced hypothermia in rat models indicate the serotonergic influence of QCM-13
for anti-depressant potential.